Why don’t Ozempic and Wegovy help everyone lose weight?

And while these drugs help curb appetite, they don’t magically eliminate temptation. After all, there’s a strong social component to eating food. “We eat because it looks good, tastes good, we’re in the company of others, or because it’s available,” Rothberg explains. A person for whom these impulses or environmental stimuli compete with the drug won’t lose as much weight as someone who doesn’t have to deal with those factors, he says.

Differences in metabolism, or how people break down food and convert it into energy, will also matter. A person’s age and hormonal function, as well as the amount of physical activity they engage in, all affect metabolism.

The researchers are also exploring whether genetic factors may explain some of the variability in responses. In 2022, Pearson and colleagues published a paper in the journal Lancet in which they identified a gene called ARRB1 which appears to be involved in glucose control. When they analyzed genetic data from more than 4,500 adults, they found that people with certain variants of this gene reported lower blood sugar levels when taking GLP-1 drugs.

General ARRB1 It is involved in recycling the GLP-1 receptor inside the cell and returning it to the cell surface. It is likely, Pearson points out, that people with these variants — about 2 or 3 percent of whites and 11 percent of Hispanics — have more of these receptors in the insulin-producing cells of the pancreas. Because GLP-1 drugs work by binding to these receptors, the greater reduction in blood glucose is due to greater binding activity, which stimulates more insulin production.

But in Pearson’s study, genetic changes were not associated with weight loss, meaning that the effect was probably limited to the pancreas. Even so, he emphasizes that it is likely that there are genetic factors that partly explain the weight-loss response. And it is possible that variants in several genes, not just one, determine how people respond differently. Pearson’s group is currently collaborating with researchers at the University of Montreal to study genetic factors and weight loss in people using GLP-1 drugs.

For some patients who don’t respond to GLP-1 treatments, another mechanism may be at work in their obesity, says Rekha Kumar, an endocrinologist and medical director of Found, a company that offers personalized weight-loss plans. “It’s possible that what’s causing them to gain weight isn’t necessarily related to the GLP-1 pathway,” he says. “They may have more success with a drug that works differently.”

Obesity “Phenotypes” for Weight Loss with GLP-1 Supplements

Mayo Clinic researchers are trying to classify people based on their obesity “phenotype,” the behavioral components that underlie the disease. Mayo Clinic gastroenterologist Andrew Acosta and colleagues used machine learning techniques to describe four main types of obesity:hungry brain (hungry brain)», in which people never feel full; «hungry bowels (hungry bowels)», in which people eat until they are full, but soon after feel hungry again;hungry emotional (emotional hunger)”, that is, people who eat to cope with emotional problems or to reward themselves, regardless of whether they are hungry; and “slow burning (slow burning)” that don’t burn calories fast enough. Acosta’s study found that people with empty bowels lost more weight when taking GLP-1 supplements than other types of people.

Patients who don’t respond well to these treatments won’t have to wait long to find other options. GLP-1 drugs are proving increasingly effective. While semaglutide targets only the GLP-1 receptor, the new tirzepatide targets GLP-1 plus another receptor, GIP (stomach inhibitory polypeptide). Drugmakers are studying whether new treatments that target more than one receptor involved in obesity can promote weight loss. “As we get more advanced in using these combinations of gut hormones, we’ll see a greater response in the population,” Kumar says.

This article was originally published in WIRED. Adapted by Andrei Osornio.